Neuroembryology as a Process of Pattern Formation PSC 113 Jeff Schank

Outline The Development of Brains A Self-Organization Perspective on the Development of the Nervous System Pattern Formation and Self-Organization Cellular Slime Molds Rules of Pattern Formation in Brains Migration Differentiation Connectivity Selective Survival

The Development of Brains Today, we will focus on how the brain develops as a self-organizing process Self-organization is a process in which components (e.g., cells) interact in relatively simple ways to generated complex patterns of organization and structure. Key features of self-organization are that The parts do not have a “blue print” or “instruction book” for how they should organize There is no overall controlling element directing the organization Complex patterns can emerge from local interactions with other cells and physicochemical properties of their substrate and context

A Self-Organization Perspective on the Development of the Nervous System There are many questions that can be asked about how such a complex system such as a brain emerges during development: How are all of the neurons generated from a single-celled embryo (i.e. zygote)? How do neural cells “know” what type they are to become? How do neurons end up in the correct spatial location in the brain? How do specific connections form among neurons?

Four Causes Composition Proximate Cause Organization Function

Pattern Formation and Self-Organization: Cellular slime molds

Dictystelium Discoideum Aggregation when starving Spiral waves via cAMP Slug stage Fruiting bodies

Embryonic Development

Gastrulation in Mammals Ectoderm (outer layer; these cells give rise to the nervous system and skin), Mesoderm (middle layer; these cells give rise to the muscle, skeleton, connective tissue, and cardiovascular and urogenital systems), and Endoderm (inner layer; these cells give rise to the gut and other internal organs)

Neurulation A groove forms along the anterior-posterior axis of the ectoderm Ectodermal cells on either side of this neural groove thicken and form the neural plate, which lies on the dorsal surface of the developing embryo As the embryo develops, the folds of the neural plate meet and cover the groove, forming the neural tube from which will emerge the brain and the spinal cord of the central nervous system During neural tube formation, some cells break away from the neural plate and move just above the top of the neural tube, forming the neural crest, which will eventually give rise to spinal and autonomic ganglia

Cell proliferation Cell proliferation begins at this point along the neural tube resulting in distinct specializations along the rostral-caudal axis Cell proliferation gives rise to specific brain divisions: prosencephalon, mesencephelon, and rhombencephelon These three structures eventually become the cerebral hemispheres, the midbrain, and the brain stem, respectively

Principles of Pattern Formation in Brains Migration After cell division (mitosis), cells (neuroblasts) that will become neurons are in many respects like the amoebae To fully develop as specific types of neurons, they must first migrate and aggregate at various locations in the developing brain Like free-living amoebae, the migrating neuroblasts extend part themselves in one direction and pull the rest of the cell in that direction As with Dictyostelium amoebae, local physical and chemotaxic interactions among neuroblasts and substrate are critical

Migration and Radial Glial Cells Radial glial (quick introduction to glial cells, also see) cells provide one mechanism by which migrating cells move to specific locations Many waves of migrating cells move up “rope” ladders For normal development to occur, earlier migrating cells must “get off” at the right place or pile ups can occur Failure to do so can lead to sever developmental abnormalities in development such as "reeler" and "staggerer" mice In humans Neuronal Migration Disorders have been identified such as Subcortical band heterotopia (video)

Migration and Radial Glial Cells

Differentiation After the amoebae like neuroblasts reach a destination in the developing nervous system they begin to differentiate into neurons and glia cells

Connectivity A functional brain are the patterns of connections formed by the axons and dendrites of developing neurons Axons and dendrites move towards targets as neurites The growth cone (video 2, 3, 4) is at the tip of neurites and it responds to cues and interactions with its local environment. In much the same way as migrating cells Nerve growth factor (NGF) can guide the direction of the neural growth cone just as cAMP guides the movement of Dictyostelium amoebae Neurites move by finger-like extensions from the growth cones, which adhere to the substrate and drag the neurite along Just as with neural selectivity and death, dendrites can be increased or decreased by the gradients of NGF surrounding a cell

Selective Survival

Summary Animation Relating Development to the Adult Brain